Abstract
Dyslipoproteinemias such as elevated LDL-cholesterol, reduced HDL-cholesterol, elevated
triglycerides and elevated lipoprotein(a) play a central role in atherosclerosis.
An elevated LDL concentration is pro-atherogenic because LDL are intimately linked
to oxidative and inflammatory processes in the arterial wall. HDL on the other hand
are anti-atherogenic because they mediate cholesterol efflux from the arterial wall,
modulate the metabolism of atherogenic lipoproteins, and directly affect endothelial
function. The current therapeutic focus is on LDL reduction and much less on HDL elevation,
although fibrates and particularly nicotinic-acid/niacin are potent drugs to increase
HDL-cholesterol and although both groups of drugs have been proven beneficial in large
end-point studies. Furthermore, new HDL raising drugs are being developed. In patients
with established atherosclerosis or at high risk for atherosclerosis statin-based
LDL reduction will remain the cornerstone of lipid therapy, but many patients may
benefit from combination therapy aiming at optimizing all lipid parameters.
Key words
HDL-cholesterol - metabolic syndrome - fibrate - nicotinic-acid - niacin
References
- 1
American Diabetes Association .
Clinical practice recommendations 2005.
Diab Care.
2005;
28 (Suppl 1)
4-37
- 2
Avorn J.
Torcetrapib and atorvastatin - should marketing drive the research agenda?.
N Engl J Med.
2005;
352
2573-2576
- 3
Barter P J, Nicholls S, Rye K A, Anantharamaiah G M, Navab M, Fogelman A M.
Antiinflammatory properties of HDL.
Circ Res.
2004;
95
764-772
- 4
BIP Study Investigation .
Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients
with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study.
Circulation.
2000;
102
21-27
- 5
Birjmohun R S, Hutten B A, Kastelein J J, Stroes E S.
Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds.
J Am Coll Cardiol.
2005;
45
185-197
- 6
Carlson L A, Rosenhamer G.
Reduction of mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention
Study by combined treatment with clofibrate and nicotinic acid.
Acta Med Scand.
1988;
223
405-418
- 7
Coronary Drug Project .
Clofibrate and niacin in coronary heart disease.
JAMA.
1975;
231
360-381
- 8
Deutsche Diabetes Gesellschaft .
Praxisleitlinien.
Diab Stoffw.
2002;
11 (Suppl 2)
3-5
- 9
Von Eckardstein A, Hersberger M, Rohrer L.
Current understanding of the metabolism and biological actions of HDL.
Curr Opin Clin Nutr Metab Care.
2005;
8
147-152
- 10
The Field Study Investigators .
The need for a large-scale trial of fenofibrate therpy in diabetes: the rationale
and design of the fenofibrate intervention and event lowering in Diabetes (FIELD)
study.
Cardiovasc Diabetol.
2004;
1-11
- 11
Frick M H, Elo O, Haapa K, Heinonen O P, Heinsalmi P, Helo P, Huttunen J K, Kaitaniemi P,
Koskinen P, Manninen V.
Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men
with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of
coronary heart disease.
N Engl J Med.
1987;
317
1237-1245
- 12
Frick M H, Syyanne M, Nieminen M S, Kauma H, Majajalme S, Virtanen V, Kesaniemi Y A,
Pasternack A, Taskinen M R.
Prevention of the angiographic progression of coronary and vein-graft atherosclerosis
by gemfibrozil after coronary bypass surgery in men with low levels of HDL cholesterol.
Lopid Coronary Angiography Trial (LOCAT) Study Group.
Circulation.
1997;
96
2137-2143
- 13
Kannel W B, Castelli W P, Gordon T.
Cholesterol in the prediction of atherosclerotic disease. New perspectives based on
the Framingham study.
Ann Intern Med.
1979;
90
85-91
- 14
Libby P, Theroux P.
Pathophysiology of coronary artery disease.
Circulation.
2005;
111
3481-3488
- 15
Linsel-Nitschke P, Tall A R.
HDL as a target in the treatment of atherosclerotic cardiovascular disease.
Nature.
2005;
4
193-205
- 16
Rubins H B, Robins S J, Collins D, Fye C L, Anderson J W, Elam M B, Faas F H, Linares E,
Schaefer E J, Schectman G, Wilt T J, Wittes J.
Gemfibrozil for the secondary prevention of coronary heart disease in men with low
levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein
Cholesterol Intervention Trial Study Group.
N Engl J Med.
1999;
341
410-418
- 17
Schatz H, Wehling M.
Fighting against the “hypertriglyceridaemic waist”: a new international institute
for the metabolic syndrome.
Exp Clin Endocrinol Diabetes.
2003;
111
119-120
- 18
Shepherd J, Betteridge J, Van Gaal L.
Nicotinic acid in the management of dyslipidaemia associated with diabetes and metabolic
syndrome: a position paper developed by a European Consensus Panel.
Curr Med Res Opin.
2005;
21
665-682
- 19
Taskinen M R.
Diabetic dyslipidemia: from basic research to clinical practise.
Diabetologia.
2003;
46
733-749
- 20
Taylor A J, Sullenberger L E, Lee H J, Lee J K, Grace K A.
Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol
(ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on
atherosclerosis progression in secondary prevention patients treated with statins.
Circulation.
2004;
110
3509-3511
- 21
Vrecer M, Turk S, Drinover J, Mrhar A.
Use of statins in primary and secondary prevention of coronary heart disease and ischemic
stroke. Meta-analysis of randomized trials.
Int J Clin Pharmacol Ther.
2003;
12
567-577
Prof. Klaus G. Parhofer MD
Medical Department II - Großhadern
University Munich
Marchioninistraße 15
81377 Munich
Germany
Phone: + 498970953010
Fax: + 49 89 70 95 88 79
Email: Klaus.Parhofer@med.uni-muenchen.de